Challenges and approaches to estimating mortality attributable to the use of selected illicit drugs

A number of unique challenges are faced when attempting to estimate mortality attributable to illicit drugs. The hidden nature of illicit drug use creates difficulties in quantifying the prevalence of such use; identifying adverse health effects associated with exposure, and calculating the risk of these effects. The use of cohort studies of drug users allows the identification of causes of mortality associated with drug use and the determination of the risk of these causes. This risk estimate can then be used in conjunction with estimates of the prevalence of drug use to, extrapolate the burden of mortality. We identify a number of such studies and present some solutions to the major challenges faced when attempting to estimate the global burden of mortality attributable to illicit drug use. Copyright (C) 2001 S. Karger AG, Basel.

Small area population disease burden

Small area health statistics has assumed increasing importance as the focus of population and public health moves to a more individualised approach of smaller area populations. Small populations and low event occurrence produce difficulties in interpretation and require appropriate statistical methods, including for age adjustment. There are also statistical questions related to multiple comparisons. Privacy and confidentiality issues include the possibility of revealing information on individuals or health care providers by fine cross-tabulations. Interpretation of small area population differences in health status requires consideration of migrant and Indigenous composition, socio-economic status and rural-urban geography before assessment of the effects of physical environmental exposure and services and interventions. Burden of disease studies produce a single measure for morbidity and mortality - disability adjusted life year (DALY) - which is the sum of the years of life lost (YLL) from premature mortality and the years lived with disability (YLD) for particular diseases (or all conditions). Calculation of YLD requires estimates of disease incidence (and complications) and duration, and weighting by severity. These procedures often mean problematic assumptions, as does future discounting and age weighting of both YLL and YLD. Evaluation of the Victorian small area population disease burden study presents important cross-disciplinary challenges as it relies heavily on synthetic approaches of demography and economics rather than on the empirical methods of epidemiology. Both empirical and synthetic methods are used to compute small area mortality and morbidity, disease burden, and then attribution to risk factors. Readers need to examine the methodology and assumptions carefully before accepting the results.

Post-traumatic stress disorder: Findings from the Australian National Survey of Mental Health and Well-being

Background. We report on the epidemiology of post-traumatic stress disorder (PTSD) in the Australian community, including information on lifetime exposure to trauma, 12-month prevalence of PTSD, sociodemographic correlates and co-morbidity. Methods. Data were obtained from a stratified sample of 10641 participants as part of the Australian National Survey of Mental Health and Well-being. A modified version of the Composite International Diagnostic Interview was used to determine the presence of PTSD, as well as other DSM-IV anxiety, affective and substance use disorders. Results. The estimated 12-month prevalence of PTSD was 1.33%, which is considerably lower than that found in comparable North American studies. Although females were at greater risk than males within the subsample of those who had experienced trauma, the large gender differences noted in some recent epidemiological research were not replicated. Prevalence was elevated among the never married and previously married respondents, and was lower among those aged over 55. For both men and women, rape and sexual molestation were the traumatic events most likely to be associated with PTSD. A high level of Axis I co-morbidity was found among those persons with PTSD Conclusions. PTSD is a highly prevalent disorder in the Australian community and is routinely associated with high rates of anxiety, depression and substance disorders. Future research is needed to investigate rates among other populations outside the North American continent.

The co-segregation of psychosis and selected physical disorders within families of patients with psychosis versus well controls

While it has been reported that individuals with psychosis are at increased or decreased risk of various physical disorders such as cancer and rheumatoid arthritis, there has been less research on the co-segregation of physical disorders within the first-degree relatives of those with psychosis compared to relatives of well controls. The aim of this study was to examine these issues in an epidemiologically informed catchment-area based case-control study. Patients with psychosis were drawn from a prevalence study undertaken as part of the Australian National Mental Health Survey. In addition, we recruited well controls who resided in the same catchment area. For each subject, we drew pedigrees and used a structured checklist to assess the presence of selected psychiatric disorders, and selected disorders such as multiple sclerosis, epilepsy, spina bifida, thyroid disorders, diabetes, asthma and eczema. Data based on pedigrees from 293 individuals with psychosis and 292 well controls was available. As expected, the odds of havingschizophrenia and affective disorders were significantly increased in the families of cases versus controls. The odds of havingeczema were significantly reduced in the relatives of those with psychosis. All other disorders occurred with equal frequency in cases versus control pedigrees. Current theories of eczema suggest that an absence of early life exposure to antigens and infectious agents may fail to prime the na¨ıve immune system, and leave the person at increased risk of eczema. The results of this study suggest that genetic andror environmental factors that facilitate psychosis may protect against eczema. The Stanley Foundation supported this project.

Paternal age as a risk factor for psychosis and schizophrenia: Findings from Denmark, Sweden and Australia

The offspringof older fathers have an increased risk of various disorders that may be due to the accumulation of DNA mutations during spermatogenesis. Previous studies have suggested increased paternal age may be a risk factor for schizophrenia. The aim of the current study was to examine paternal age as a risk factor for schizophrenia andror psychosis. We used data from three sources: a population-based cohort studyŽDenmark., and two case-control studiesŽSweden and Australia.. In the Danish and Australian studies, we examined both psychosis and schizophrenia. In the Swedish study we examined psychosis only. After controllingfor the effect of maternal age, increased paternal age was significantly associated with increased risk of both psychosis and schizophrenia in the Danish study and of psychosis in the Swedish study. The Australian study found no association between paternal age and risk of psychosis or schizophrenia. In all three studies the relationship between paternal age and risk of disorder in the offspring was AUB-shaped. In addition to an increased risk for the offspringof older father Ž)35 years., there was a non-significant increase for the offspringof fathers aged less than 20 years. The possible role of paternally derived DNA mutations andror other psychosocial factors associated with older paternal age warrants further research. The ‘U’-shaped relationship suggests that factors other than DNA mutations may warrant consideration in this research. The Stanley Foundation supported this project.

Perioperative epidural analgesia and outcome after major abdominal surgery in high-risk patients

In a primary analysis of a large recently completed randomized trial in 915 high-risk patients undergoing major abdominal surgery, we found no difference in outcome between patients receiving perioperative epidural analgesia and those receiving IV opioids, apart from the incidence of respiratory failure. Therefore, we performed a selected number of predetermined subgroup analyses to identify specific types of patients who may have derived benefit from epidural analgesia. We found no difference in outcome between epidural and control groups in subgroups at increased risk of respiratory or cardiac complications or undergoing aortic surgery, nor in a subgroup with failed epidural block (all P > 0.05). There was a small reduction in the duration of postoperative ventilation (geometric mean [SD]: control group, 0.3 [6.5] h, versus epidural group, 0.2 [4.8] h, P = 0.048). No differences were found in length of stay in intensive care or in the hospital. There was no relationship between frequency of use of epidural analgesia in routine practice outside the trial and benefit from epidural analgesia in the trial. We found no evidence that perioperative epidural analgesia significantly influences major morbidity or mortality after major abdominal surgery.

Effects of alcohol exposure during early life on neuron numbers in the rat hippocampus. I. Hilus neurons and granule cells

We previously showed that 16-day-old rats exposed to a relatively high dose of ethanol at 10-15 postnatal days of age have fewer neurons in the hilus region of the hippocampus compared with controls. Dentate gyrus granule cell numbers, however, showed no statistically significant changes attributable to the ethanol treatment. It is possible that some of the changes in brain morphology, brought about as a result of the exposure to ethanol during early life, may not be manifested until later in life. This question has been further addressed in an extension to our previous study. Wistar rats were exposed to a relatively high daily dose of ethanol on postnatal days 10-15 by placement in a chamber containing ethanol vapour, for 3 h/day. The blood ethanol concentration was found to be similar to430 mg/dl at the end of the period of exposure. Groups of ethanol-treated (ET), separation control (SC), and mother-reared control (MRC) rats were anaesthetised and killed either at 16 or 30 days of age by perfusion with phosphate-buffered 2.5% glutaraldehyde. The Cavalieri principle and the physical disector methods were used to estimate, respectively, the regional volumes and neuron cell numerical densities in the hilus and granule cell regions of the dentate gyrus. The total numbers of neurons in the hilus region and granule cell layer were computed from these estimates. It was found that 16-day-old animals had 398,000-441,000 granule cells, irrespective of group. The numbers of granule cells increased such that by 30 days of age, rats had 487,000-525,500 granule cells. However, there were no significant differences between ethanol-treated rats and their age-matched controls in granule cell numbers. In contrast, ethanol-treated rats had slightly but significantly fewer neurons in the hilus region than did control animals at 16 days of age, but not at 30 days of age. Therefore, it appears that a short period of ethanol exposure during early life can have effects on neuron numbers of some hippocampal neurons, but not others. The effects on hilar neuron numbers, observed as a result of such short periods of ethanol treatment, appeared to be transitory. (C) 2003 Wiley-Liss, Inc.

Background risk in generalized expected utility theory

In this paper, it is shown that, for a wide range of risk-averse generalized expected utility preferences, independent risks are complementary, contrary to the results for expected utility preferences satisfying conditions such as proper and standard risk aversion.

Ten-year risk of first recurrent stroke and disability after first-ever stroke in the Perth Community Stroke Study

Background and Purpose-Limited information exists on the long-term prognosis after first-ever stroke. We aimed to determine the absolute frequency of first recurrent stroke and disability and the relative frequency of recurrent stroke over 10 years after first-ever stroke in Perth, Western Australia. Methods-For a 12-month period beginning February 1989, all individuals with suspected acute stroke or transient ischemic attack who lived in a geographically defined and representative region of Perth were registered prospectively. Patients with a definite first-ever stroke were followed up 10 years after the index event. Results-Over 10 years of follow-up, the cumulative risk of a first recurrent stroke was 43% (95% confidence interval [CI], 34 to 51). After the first year after first-ever stroke, the average annual risk of recurrent stroke was approximate to4%. Case fatality at 30 days after first recurrent stroke was 41%, which was significantly greater than the case fatality at 30 days after first-ever stroke (22%) (P=0.003). For 30-day survivors of first-ever stroke, the 10-year cumulative risk of death or new institutionalization was 79% (95% CI, 73 to 85) and of death or new disability was 87% (95% CI, 81 to 92). Conclusions-Over 10 years of follow-up, the risk of first recurrent stroke is 6 times greater than the risk of first-ever stroke in the general population of the same age and sex, almost one half of survivors remain disabled, and one seventh require institutional care. Effective strategies for prevention of stroke need to be implemented early, monitored frequently, and maintained long term after first-ever stroke.